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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Khallou-laschet, Jamila Morvan, Marion Fornasa, Giulia Nicoletti, Antonino Gaston, Anh-thu Guedj, Kevin Caligiuri, Giuseppina Ben Mkaddem, Sanae Clement, Marc |
| Description | Author Affiliation: Clement M ( Institut National de la Santé et de la Recherche Médicale (INSERM), U1148, Laboratory of Vascular Translational Science, Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, and Département Hospitalo-Universitaire (DHU) Fibrosis, Inflammation, and Remodeling (FIRE), F-75018 Paris, France.); |
| Abstract | CD31 is a transhomophilic tyrosine-based inhibitory motif receptor and is expressed by both dendritic cells (DCs) and T lymphocytes. Previous studies have established that the engagement of CD31 drives immune-inhibitory signaling in T lymphocytes, but the effect exerted by CD31 signaling in DCs remains elusive. Here, we show that CD31 is a key coinhibitory receptor on stimulated DCs, favoring the development of tolerogenic functions and finally resulting in T-cell tolerance. The disruption of CD31 signaling favored the immunogenic maturation and migration of resident DCs to the draining lymph nodes. In contrast, sustaining the CD31/SHP-1 signaling during DC maturation resulted in reduced NF-κB nuclear translocation, expression of costimulatory molecules, and production of immunogenic cytokines (e.g., IL-12, IL-6), whereas the expression of TGF-β and IL-10 were increased. More importantly, CD31-conditioned DCs purified from the draining lymph nodes of ovalbumin-immunized mice favored the generation of antigen-specific regulatory T cells $(CD25^{+}$ forkhead box $P3^{+})$ at the expense of effector $(IFN-γ^{+})$ cells upon coculture with naive ovalbumin-specific $CD4^{+}$ T lymphocytes ex vivo. Finally, the adoptive transfer of CD31-conditioned myelin oligodendrocyte glycoprotein-loaded DCs carried immune tolerance against the subsequent development of MOG-induced experimental autoimmune encephalomyelitis in vivo. The key coinhibitory role exerted by CD31 on DCs highlighted by the present study may have important implications both in settings where the immunogenic function of DCs is desirable, such as infection and cancer, and in settings where tolerance-driving DCs are preferred, such as autoimmune diseases and transplantation. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 12 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antigens, CD31 Immunology Dendritic Cells Animals Genetics Cell Differentiation Cell Movement Cytology Flow Cytometry Immunophenotyping Mice Mice, Inbred C57BL Mice, Knockout Signal Transduction Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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